EP2324053B1 - Ferritine 2 destinée à l'immunisation d'un hôte contre les tiques - Google Patents

Ferritine 2 destinée à l'immunisation d'un hôte contre les tiques Download PDF

Info

Publication number
EP2324053B1
EP2324053B1 EP09768811.3A EP09768811A EP2324053B1 EP 2324053 B1 EP2324053 B1 EP 2324053B1 EP 09768811 A EP09768811 A EP 09768811A EP 2324053 B1 EP2324053 B1 EP 2324053B1
Authority
EP
European Patent Office
Prior art keywords
ferritin
fer2
tick
amino
host
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
EP09768811.3A
Other languages
German (de)
English (en)
Other versions
EP2324053A2 (fr
Inventor
Petr Kopacek
Ondrej Hajdusek
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Biologicke Centrum AV CR V V I Ustav Molekularni Biologie Rostlin
Original Assignee
Biologicke Centrum AV CR V V I Ustav Molekularni Biologie Rostlin
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Biologicke Centrum AV CR V V I Ustav Molekularni Biologie Rostlin filed Critical Biologicke Centrum AV CR V V I Ustav Molekularni Biologie Rostlin
Publication of EP2324053A2 publication Critical patent/EP2324053A2/fr
Application granted granted Critical
Publication of EP2324053B1 publication Critical patent/EP2324053B1/fr
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/43504—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates
    • C07K14/43513—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from arachnidae
    • C07K14/43527—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from arachnidae from ticks
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/14—Ectoparasiticides, e.g. scabicides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies

Definitions

  • a protein antigen for immunization of the organism - the produced antibody will block an iron transport in the tick body and hereby prevent its long-lasting feeding on the host, eventually block transmission of pathogens from the tick to the host.
  • Tick ferritin 1 is post-trascriptionally regulated by the IRP (iron-regulatory protein), which binds IRE (iron-responsive element) loop of the particular mRNA.
  • IRP iron-regulatory protein
  • IRE iron-responsive element
  • Ferritin 1 is an oligomer (composed of 24 subunits) and functions in the intracellular iron storage and prevention of the undesirable oxidative effects caused by the free iron.
  • Ixodes scapularis 1108462734296 genomic scaffold, whole genome shotgun sequence XP002562989 retrieved from EBPI accession no. EMBL:DS954460
  • Database accession no. DS954460 discloses the whole genome shotgun sequence of Ixodes scapularis comprising 87576 bp.
  • ferritins 1 which are intracellular ferritins having the function of iron storage.
  • Ferritin 2 is a newly identified and characterized protein, which is secreted into the tick plasma. It has been identified in ticks Ixodes ricinus, Ixodes scapularis, Dermacentor variabilis, and Rhipicephalus microplus (formerly Boophilus microplus). We have sequenced these ferritins and determined their primary structures. Ferritin 2 functions in the- tick body as a transporter of iron, which is obtained from the host blood (plasma). When we succeed to block the protein, the attached tick will not be able to feed on the host, because the mechanism of non-heme iron transport from the gut to the peripheral tissue will not be functional, which is essential for tick parasitic life.
  • ferritin 2 The blocking of ferritin 2 can be achieved by the reaction with the specific antibody, what leads to the formation of immunocomplex. Specific antibodies will be raised up in the host organism after immunization with the tick antigen ferritin 2.
  • a recombinant ferritin 2 or its fragment expressed in the prokaryotic ( Escherichia coli, etc.), or eukaryotic ( Pichia pastoris, insect cells, etc.) expression systems can be used as a suitable antigen for the immunization.
  • Expressed and purified recombinant ferritin 2 could be used for immunization with the appropriate adjuvants or formulation media.
  • the advantage of use of ferritin 2 is its substantial amino-acid sequence difference from the mammalian heavy (H) or light (L) chain ferritins. This substantially reduces a risk of undesirable side effects of the vaccine after the host immunization.
  • Ticks with decreased synthesis of ferritin 2, caused by RNA interference, are not able to finish their feeding and usually dry and die directly on the host. This fact makes ferritin 2 an ideal candidate for development of vaccine or other compound that will interfere with ferritin 2. Disruption of the tick feeding on the immunized host can impair the normal tick development and possibly will lead to the elimination of pathogen transmission by ticks (e.g., Lyme disease spirochetes), which are dependent on the successful tick feeding.
  • ticks e.g., Lyme disease spirochetes
  • Ferritin 2 designated as FER2-IR, is a protein produced by the tick Ixodes ricinus and its primary structure is determined by the amino-acid sequence:
  • the signal sequence responsible for the protein secretion of the cell is marked in bold.
  • the primary sequence enables correct folding of the protein to the quarter structure, which transports the non-heme iron from the tick gut to the peripheral tissues. In the absence of ferritin 2, or in the case of its successful blocking, the ticks are not able to finish feeding and dry directly on the host.
  • Ferritin 2 designated as FER2-IS, is a protein produced by the tick Ixodes scapularis and its primary structure is determined by the amino-acid sequence.
  • the signal sequence responsible for the protein secretion of the cell is marked in bold.
  • the primary sequence enables correct folding of the protein to the quarter structure, which transports the non-heme iron from the tick gut to the peripheral tissues. In the absence of ferritin 2, or in the case of its successful blocking, the ticks are not able to finish feeding and dry directly on the host.
  • Ferritin 2 designated as FER2-RM, is a protein produced by the tick Rhipicephalus microplus and its primary structure is determined by the amino-acid sequence:
  • the signal sequence responsible for the protein secretion of the cell is marked in bold.
  • the primary sequence enables correct folding of the protein to the quarter structure, which transports the non-heme iron from the tick gut to the peripheral tissues. In the absence of ferritin 2, or in the case of its successful blocking, the ticks are not able to finish feeding and dry directly on the host.
  • Ferritin 2 designated as FER2-DV, is a protein produced by the tick Dermacentor variabilis and its primary structure is determined by the amino-acid sequence:
  • the signal sequence responsible for the protein secretion of the cell is marked in bold.
  • the primary sequence enables correct folding of the protein to the quarter structure, which transports the non-heme iron from the tick gut to the peripheral tissues. In the absence of ferritin 2, or in the case of its successful blocking, the ticks are not able to finish feeding and dry directly on the host.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Insects & Arthropods (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Veterinary Medicine (AREA)
  • Toxicology (AREA)
  • Biochemistry (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Animal Behavior & Ethology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Claims (5)

  1. Ferritine 2 pour l'immunisation de l'hôte contre les tiques qui a la séquence d'acides aminés sans la séquence signal dans au moins 85% identique à la séquence d'acides aminés de la ferritine 2 d'Ixodes ricinus (FER2-IR)
    Figure imgb0017
    ou la ferritine 2 d'Ixodes scapularis (FER2-IS)
    Figure imgb0018
    ou la ferritine 2 de Rhipicephalus microplus (FER2-RM)
    Figure imgb0019
    ou la ferritine 2 de Dermacentor variabilis (FER2-DV)
    Figure imgb0020
    et dans les conditions natives, elle forme la structure quaternaire, qui transporte le fer non hémique de l'intestin de la tique dans les tissus périphériques.
  2. Ferritine 2 pour l'immunisation de l'hôte contre les tiques selon la revendication 1, qui a la structure primaire sans séquence signal composée d'une séquence d'acides aminés de la ferritine 2 d'Ixodes ricinus (FER2-IR).
  3. Ferritine 2 pour l'immunisation de l'hôte contre les tiques selon la revendication 1, qui a la structure primaire sans séquence signal composée d'une séquence d'acides aminés de la ferritine 2 d'Ixodes scapularis (FER2-IS).
  4. Ferritine 2 pour l'immunisation de l'hôte contre les tiques selon la revendication 1, qui a la structure primaire sans séquence signal composée d'une séquence d'acides aminés de la ferritine 2 de Rhipicephalus microplus (FER2-RM).
  5. Ferritine 2 pour l'immunisation de l'hôte contre les tiques selon la revendication 1, qui a la structure primaire sans séquence signal composée d'une séquence d'acides aminés de la ferritine 2 de Dermacentor variabilis (FER2-DV).
EP09768811.3A 2008-06-25 2009-06-18 Ferritine 2 destinée à l'immunisation d'un hôte contre les tiques Active EP2324053B1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CZ20080402A CZ301541B6 (cs) 2008-06-25 2008-06-25 Feritin 2 pro imunizaci organismu proti klíštatum
PCT/CZ2009/000085 WO2009155886A2 (fr) 2008-06-25 2009-06-18 Ferritine 2 destinée à l'immunisation d'un hôte contre les tiques

Publications (2)

Publication Number Publication Date
EP2324053A2 EP2324053A2 (fr) 2011-05-25
EP2324053B1 true EP2324053B1 (fr) 2015-08-12

Family

ID=41445006

Family Applications (1)

Application Number Title Priority Date Filing Date
EP09768811.3A Active EP2324053B1 (fr) 2008-06-25 2009-06-18 Ferritine 2 destinée à l'immunisation d'un hôte contre les tiques

Country Status (7)

Country Link
US (1) US8168763B2 (fr)
EP (1) EP2324053B1 (fr)
AU (1) AU2009264468A1 (fr)
BR (1) BRPI0914673A2 (fr)
CZ (1) CZ301541B6 (fr)
MX (1) MX341928B (fr)
WO (1) WO2009155886A2 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP6327699B2 (ja) * 2014-02-28 2018-05-23 国立大学法人 鹿児島大学 抗マダニワクチン
CA3095174A1 (fr) * 2018-04-03 2019-10-10 Sanofi Polypeptides ospa antigeniques

Also Published As

Publication number Publication date
CZ301541B6 (cs) 2010-04-07
CZ2008402A3 (cs) 2010-01-06
WO2009155886A3 (fr) 2010-04-08
BRPI0914673A2 (pt) 2016-05-17
MX2011000003A (es) 2011-06-01
WO2009155886A2 (fr) 2009-12-30
AU2009264468A1 (en) 2009-12-30
EP2324053A2 (fr) 2011-05-25
US8168763B2 (en) 2012-05-01
MX341928B (es) 2016-09-08
US20110118449A1 (en) 2011-05-19

Similar Documents

Publication Publication Date Title
US20140213514A1 (en) Insulin production methods and pro-insulin constructs
JP6077027B2 (ja) 精製生物活性異種タンパク質を得る方法
WO2010144502A2 (fr) Polypeptides d'hormone de croissance et leurs procédés de production et d'utilisation
DK159856B (da) Humaninsulinderivater og farmaceutiske praeparater, som indeholder disse derivater
KR20180005249A (ko) 병리학적 석회화 병태를 치료하기 위한 조성물, 및 이의 사용 방법
JP2002538824A (ja) 組換えペプチド産生のための改善された方法
EP2324053B1 (fr) Ferritine 2 destinée à l'immunisation d'un hôte contre les tiques
Srinivasulu et al. Expression, purification and structural characterization of recombinant hepcidin, an antimicrobial peptide identified in Japanese flounder, Paralichthys olivaceus
CN102282260A (zh) 用于制备人重组胰岛素的方法
EP1194445B1 (fr) Methodes de purification de proteines recombinantes antagonistes de l'hormone de croissance par extraction biphasee aqueuse
US9408896B2 (en) Vaccination of companion animals to elicit a protective immune response against tick infestations and tick-borne pathogen transmission
EP2853270B1 (fr) Vaccin recombinant contre le coryza infectieux aviaire et son procédé de préparation
US9453058B2 (en) Variants of the major allergen Phl P 1 from timothy grass
US9556244B2 (en) Vaccination of animals to elicit a protective immune response against tick infestations and tick-borne pathogen transmission
Wong et al. Location and reduction of icarapin antigenicity by site specific coupling to polyethylene glycol
JP4809242B2 (ja) 新規なｃｃ−ケモカイン結合タンパク質
US10363292B2 (en) Vaccination with anti-tick antigens to control multiple tick species and disease transmission in white-tailed deer and other host animals
CN111848774A (zh) 一种美曲普汀的制备方法
US20140221606A1 (en) Aspart Proinsulin Compositions and Methods of Producing Aspart Insulin Analogs
Saouros et al. High-level bacterial expression and purification of apicomplexan micronemal proteins for structural studies
EP0857732A1 (fr) Proteine humaine analogue a la pec-60 et adn qui la code
Subramaniam et al. Molecular cloning, characterization and in vitro expression of SERPIN B1 of bighorn sheep (Ovis canadensis) and domestic sheep (Ovis aries), and comparison with that of other species
CN114651005A (zh) 生产和使用重组α1-抗胰蛋白酶(AAT)及其组合物的方法
Wei-Dong et al. Cloning and Expression of Oreochromis aurea Gonadotropin Releasing Hormone cDNA in Escherichia coli and Its Immunogenicity for Mice
AT401179B (de) Rekombinantes dna-molekül für allergene des erlenpollens, damit hergestellte proteine bzw. polypeptide, sowie deren anwendung

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20110125

AK Designated contracting states

Kind code of ref document: A2

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO SE SI SK TR

AX Request for extension of the european patent

Extension state: AL BA RS

DAX Request for extension of the european patent (deleted)
17Q First examination report despatched

Effective date: 20120717

17Q First examination report despatched

Effective date: 20120913

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

INTG Intention to grant announced

Effective date: 20150330

GRAS Grant fee paid

Free format text: ORIGINAL CODE: EPIDOSNIGR3

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO SE SI SK TR

REG Reference to a national code

Ref country code: GB

Ref legal event code: FG4D

REG Reference to a national code

Ref country code: CH

Ref legal event code: EP

REG Reference to a national code

Ref country code: AT

Ref legal event code: REF

Ref document number: 742071

Country of ref document: AT

Kind code of ref document: T

Effective date: 20150815

REG Reference to a national code

Ref country code: IE

Ref legal event code: FG4D

REG Reference to a national code

Ref country code: DE

Ref legal event code: R096

Ref document number: 602009032870

Country of ref document: DE

REG Reference to a national code

Ref country code: LT

Ref legal event code: MG4D

REG Reference to a national code

Ref country code: AT

Ref legal event code: MK05

Ref document number: 742071

Country of ref document: AT

Kind code of ref document: T

Effective date: 20150812

REG Reference to a national code

Ref country code: NL

Ref legal event code: MP

Effective date: 20150812

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150812

Ref country code: GR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20151113

Ref country code: FI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150812

Ref country code: NO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20151112

Ref country code: LV

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150812

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20151212

Ref country code: PT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20151214

Ref country code: HR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150812

Ref country code: PL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150812

Ref country code: AT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150812

Ref country code: SE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150812

Ref country code: ES

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150812

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: NL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150812

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: CZ

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150812

Ref country code: SK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150812

Ref country code: EE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150812

Ref country code: IT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150812

Ref country code: DK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150812

REG Reference to a national code

Ref country code: DE

Ref legal event code: R097

Ref document number: 602009032870

Country of ref document: DE

REG Reference to a national code

Ref country code: FR

Ref legal event code: PLFP

Year of fee payment: 8

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: RO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150812

PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT

26N No opposition filed

Effective date: 20160513

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150812

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: BE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150812

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MC

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150812

REG Reference to a national code

Ref country code: CH

Ref legal event code: PL

REG Reference to a national code

Ref country code: IE

Ref legal event code: MM4A

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: CH

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20160630

Ref country code: LI

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20160630

REG Reference to a national code

Ref country code: FR

Ref legal event code: PLFP

Year of fee payment: 9

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20160618

REG Reference to a national code

Ref country code: GB

Ref legal event code: 732E

Free format text: REGISTERED BETWEEN 20171214 AND 20171222

REG Reference to a national code

Ref country code: DE

Ref legal event code: R081

Ref document number: 602009032870

Country of ref document: DE

Owner name: VIRBAC, FR

Free format text: FORMER OWNER: BIOLOGY CENTRE AS CR, V.V.I., CESKE BUDEJOVICE, CZ

REG Reference to a national code

Ref country code: FR

Ref legal event code: PLFP

Year of fee payment: 10

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: CY

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150812

Ref country code: HU

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT; INVALID AB INITIO

Effective date: 20090618

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MT

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20160630

Ref country code: LU

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20160618

Ref country code: TR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150812

Ref country code: MK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150812

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: BG

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150812

REG Reference to a national code

Ref country code: FR

Ref legal event code: CD

Owner name: VIRBAC, FR

Effective date: 20180628

Ref country code: FR

Ref legal event code: TP

Owner name: VIRBAC, FR

Effective date: 20180628

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GB

Payment date: 20220520

Year of fee payment: 14

Ref country code: FR

Payment date: 20220519

Year of fee payment: 14

Ref country code: DE

Payment date: 20220518

Year of fee payment: 14

REG Reference to a national code

Ref country code: DE

Ref legal event code: R119

Ref document number: 602009032870

Country of ref document: DE

GBPC Gb: european patent ceased through non-payment of renewal fee

Effective date: 20230618

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: DE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20240103

Ref country code: GB

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20230618